1. Field of the Invention
The present invention provides prostamide receptor antagonists, e.g. prostamide F2α, receptor antagonists.
2. Description of Related Art
Prostamides are disclosed in U.S. Pat. No. 6,395,787, hereby incorporated by reference in its entirety, as useful to lower elevated intraocular pressure and for treating glaucoma. These compounds are structurally related to prostaglandins, e.g. Prostaglandin F2α, which are also useful in lowering elevated intraocular pressure, but prostamides do not act through the FP receptor to lower intraocular pressure. As such, prostamides do not have the same effects as prostaglandins when utilized to treat elevated intraocular pressure and/or glaucoma. For example, it has been demonstrated that bimatoprost, a synthetic analog of prostamide F2α, lowers intraocular pressure in patients unresponsive to the synthetic prostaglandin F2α analog latanoprost (Gandolfi and Cimino, Ophthalmology 110:609, 2003).
It would be desirable to have prostamide receptor antagonists to assist in pharmacologically defining prostamide receptors to aid in determining compounds which have activity at the prostamide receptor. Heretofore, compounds having prostamide receptor antagonist activity have been unknown.
Prostaglandin F2α antagonists are reported in U.S. Pat. Nos. 4,632,928; 5,747,660; and 5,955,575. The PGF2α antagonists of U.S. Pat. No. 4,632,928 are pyrazole derivatives having an ergoline skeleton. The PGF2α antagonist of U.S. Pat. No. 5,747,660 is a prostaglandin F2α receptor regulatory protein (FPRP) which is able to inhibit the binding of PGF2α to its receptor.
Novel prostaglandin F2α antagonists are reported in U.S. Pat. Nos. 6,369,089; 6,407,250; 6,509,364 and 6,511,999 which are hereby incorporated by reference in their entirety.
Interphenylene 7-Oxabicyclo [2.2.1] heptane oxazoles, useful as Thromboxane A2 receptor antagonists are reported in U.S. Pat. Nos. 5,100,889 and 5,153,327, European Patent Application 0 391 652 and J. Med. Chem. 1993, 36, 1401–1417.
Thromboxane A2 receptor antagonists, e.g. 7-oxabicycloheptyl substituted heterocyclic amide prostaglandin analogs, alone, or in combination with anti-inflammatory agents are useful in treating ulcerative gastrointestinal conditions and dysmenorrhea as disclosed in European Patent Application 0 448 274 and U.S. Pat. No. 5,605,917.